The topology and functionally important conformational changes of acetylcholine receptor, Na+/K+-transporting ATPase, and anion carrier, three proteins in the plasma membranes of animal cells, are being examined with protein chemical and immunochemical techniques. Sealed right-side-out vesicles or intact cells are used to determine on which side of the plasma membrane particular amino acids in these proteins are located. The outcome of the modification of these amino acids with reagents impermeant to the vesicles or the cells is being established by isolating peptides containing the modified amino acids by immunoadsorbents. Changes in the rate of modification of particular amino acids in anion carrier by neutral or charged electrophiles will be monitored as the conformations of the native protein are changed. The changes in rate will be followed by isolating modified peptides by immuno-adsorption. These results will implicate particular locations in this protein in functionally important structural changes. The topology of acetylcholine receptor will be correlated with recent high resolution structures of the protein.